1. Field of the Invention
The invention relates generally to a fluid resuscitation composition useful for treatment of circulatory and ischemic shock. In particular, the composition is a hypertonic solution prepared from sodium acetate and sodium chloride which provides isochloremic resuscitation. Beneficial effects from administration are obtained rapidly, resulting in large increases in cardiac output and oxygen delivery to tissues. Consequences are increased arterial pressure minimally compatible with maintenance of adequate blood supply to body organs and tissues while minimizing increased blood loss associated with higher increases in arterial pressure.
2. Description of Related Art
Circulatory shock is a common life threatening pathophysiological state which occurs secondary to trauma, hemorrhage, burns, sepsis, allergic reactions and heart failure. These different types of circulatory shock are characterized by reduced blood pressure and cardiac output with a resultant reduction in blood flow and oxygen delivery to vital organs and tissues. This low blood flow condition causes local hypoxia, ischemia, and can lead to loss of cellular and organ function and even death. Accepted definitive treatment for some types of circulatory shock and useful therapy in all types of shock are volume infusions.
The standard of care in initial management of hemorrhagic shock is rapid administration of large volumes of isotonic crystalloid solution, several liters in an adult patient. The preferred fluid is Ringer's lactate, although normal saline or other similar isotonic crystalloid solutions are also used. Recommended continued treatment is based on the observed response to the initial fluid therapy (American College of Surgeons, 1988). As a general rule, guidelines are based on the "three for one" rule. This is based on the long-standing empirical observation that most hemorrhagic shock patients require up to 300 ml of electrolyte solution for each 100 ml of blood lost.
Other isotonic fluid replacement solutions have been used, including isotonic crystalloid solutions mixed with macromolecular solutions of plasma proteins or synthesized molecules with similar oncotic properties (colloids); including albumin, dextran, hetastarch or polygelatin in 0.9% NaCl. Whole blood is also used, but it is expensive, often unavailable and cross matching may delay therapy.
Crystalloids and colloids have been used as volume expanders, but generally must be infused in large volume. Such large volumes may cause peripheral and pulmonary edema. Additionally, the large volume requirements of isotonic fluids means that there are time delays and logistic difficulties associated with vascular delivery of effective therapy.
Hyperosmotic crystalloid and hyperosmotic/hyperoncotic (crystalloid/colloid) formulations offer some physiological benefits for the treatment of circulatory shock, including improved efficacy for restoration of overall cardiovascular function in animals and man compared to conventional resuscitation (Cone et al., 1987). Normalization of circulatory function has been obtained with such solutions (Kramer and Holcroft, 1990). Small volumes of salt/concentrated dextran formulations have been shown to rapidly restore and sustain normalization of circulatory function in hemorrhage (Kramer et al., 1986; Velasco et al., 1987). However, there remain some important limitations/side effects.
Hypertonic saline infusions in shocked animals and patients have been shown to cause an initial acidosis and hypokalemia. Treatment with hypertonic saline can also lead to a hyperchloremic acidosis, possibly due to excessive chloride load. Some isotonic Ringers solutions and mildly hypertonic formulations mimic sodium and chloride concentration ratios found in plasma and are thought to decrease the likelihood of acidosis (Fox, 1976). Circulatory shock is often associated with an acidosis and thus increased acidotic insult may be deleterious.
Although hypertonic saline rapidly improves both blood pressure and cardiac output, these beneficial effects may be overshadowed by deleterious effects from increased blood pressure. Uncontrolled internal bleeding in trauma patients may be aggravated by increased pressure, leading to increased bleeding. Return of normal blood pressure resulting in increased bleeding due to arterial pressure increase may lead to increased mortality over no treatment. Therefore, ideal pre-hospital resuscitation would increase cardiac output but only modestly increase blood pressure.
Another aspect of resuscitation fluids is their use under less than ideal (non hospital) conditions. Logistic restraints may severely curtail transportation of weighty or voluminous material. In battlefield situations it may be impractical to administer large volumes, yet there is a critical need to rapidly restore oxygen delivery to critical organs and to prevent or reverse the effects of traumatic shock.